Abstract

3630

Caveolin-1 (CAV1), an essential structural constituent of caveolae that plays an important role in cellular process such as transport and signaling, has been implicated in the development of several human cancers, including lung. Recently, CAV1 gene expression was detected reduced or absent in 95% of small cell lung carcinomas (SCLC) whereas it was retained in 76% of non-small cell lung carcinoma (NSCLC; squamous cell and adenocarcinoma) cell lines, suggesting that CAV1 acts like a tumor suppressor gene in SCLC, where it appears to be required for survival and growth of NSCLC. To better understand the pathogenesis of Caveolin-1 in the pathogenesis of lung cancers, we investigated its cytoplasmic immunohistochemical expression in 411 surgically resected and paraffin-embedded lung cancers placed in tissue microarrays, including 268 adenocarcinomas, 119 squamous cell carcinomas, and 24 SCLCs. In addition, 183 normal bronchial epithelia (n=33) and squamous preneoplastic lesions (n=150) adjacent to NSCLCs were examined. The major findings were as follows: a) While high level of cytoplasmic immunohistochemical expression of Caveolin-1 was detected in NSCLC specimens, no expression was detected in all SCLCs examined. b) In NSCLCs, the mean level of expression was significantly (p<0.0001) higher in squamous cell carcinomas compared to adenocarcinomas. c) In adenocarcinomas, significant correlation between Caveolin-1 expression and smoking history was detected, with never smokers exhibiting significant lower levels compared to current smokers (p<0.025). d) No correlation between lung cancer stage and overall survival and Caveolin-1 expression was found. e) Histologically normal epithelium from NSCLC patients demonstrated a relatively high level of Caveolin-1 expression, and higher levels were detected in high-grade squamous dysplasias compared to low-grade dysplasias and squamous metaplasia. Our findings confirm and extend previous observations in lung cancer cell lines that differential expression in Caveolin-1 is detected between SCLC and NSCLC, and suggest different effect of smoking in Caveolin-1 expression among the different lung normal and neoplastic cells. In addition, caveolin-1 over-expression is a frequent and early event in the pathogenesis of lung squamous cell carcinomas. Supported by grants NIH SPORE P50CA70907 and The VITAL Department of Defense grant W81XWH-04-1-0142.